多西他赛联合照射对人胃癌裸鼠移植瘤生物效应的实验研究

Effects of docetaxel combined with radiotherapy on gastric cancer xenograft in nude mice

目的:观察多西他赛对人胃癌裸鼠移植瘤的放射增敏作用和多西他赛联合放射对肿瘤细胞凋亡的影响。方法:建立人AGS胃癌裸鼠移植瘤动物模型28只,随机分为4组:对照组、单纯照射组、单纯多西他赛组、多西他赛+照射组。测量各组移植瘤体积,计算各组抑瘤率,评价多西他赛的放射增敏效果,并对标本进行光镜观察及原位末段标记(TUNEL)检测。结果:28只裸鼠的成瘤率为100%,实验期间无死亡,比较各组移植瘤体积差异有统计学意义(P<0.01)。各组抑瘤率分别为单纯照射组36.4%,单纯多西他赛组44.2%,多西他赛+照射组86.9%。多西他赛对放射治疗的增敏值(enhancement factor,EF)值为1.5。多西他赛+照射组的平均凋亡指数(AI)为(15.6±2.3)%,与其它各组比较差异有统计学意义(P<0.01)。结论:多西他赛对人AGS胃癌裸鼠移植瘤有良好的放射增敏作用,多西他赛联合放疗能更有效地诱导肿瘤细胞凋亡。

Objective To investigate the radiosensitizing effect of docetaxel on gastric cancer xenograft in nude mice and the induction of apoptosis by docetaxel combined with radiotherapy. Methods The animal models of xenotransplanted human gastric cancer cell line AGS was set up in 28 nude mice which were divided into 4 groups at random. ：the control group,radiation group, docetaxel group and docetaxel plus radiation group. The tumor mass volume was observed in all the groups and the inhibition rate for tumor growth calculated, The effect of radiation enhancement of docetaxel was assessed.The specimens obtained from the nude mice were then detected by optical microscope and TdT- mediated dUTP nick end labeling （TUNEL）. Results The mass of gastric tumor was formed in all the nude mice,and none of the mice died.The difference in the volume of tumor formation was significant between the groups, P〈0.01. The rate of tumor inhibition in the radiation group, docetaxel group and docetaxel plus radiation group were 36.4%,44.2%, 86.9%,respectively.EF（enhancement factor） was 1.5 in the docetaxel plus radiation group.The average apoptosis index（AI） in the docetaxel plus radiation group was （15.6±2.3）%,which was higher than the other groups （P〈0.01）. Conclusions Docetaxel has an evident radiosensitizing effect on gastric cancer xenograft in the nude mice. As compared to docetaxel alone or radiation alone, docetaxel combined with radiotherapy is more efficient in inducing tumor cell apoptosis.